HI Narrow Self-Absorption in Dark Clouds: Correlations with Molecular Gas and Implications for Cloud Evolution and Star Formation

We present the results of a comparative study of HI narrow self-absorption (HINSA), OH, 13CO, and C18O in five dark clouds. The HINSA follows the distribution of the emission of the carbon monoxide isotopologues, and has a characteristic size close to that of 13CO. This confirms that the HINSA is produced by cold HI which is well mixed with molecular gas in well-shielded regions. The ratio of the atomic hydrogen density to total proton density for these sources is 5 to 27 x 10^{-4}. Using cloud temperatures and the density of HI, we set an upper limit to the cosmic ray ionization rate of 10^{-16} s^{-1}. Comparison of observed and modeled fractional HI abundances indicates ages for these clouds to be 10^{6.5} to 10^{7} yr. The low values of the HI density we have determined make it certain that the time scale for evolution from an atomic to an almost entirely molecular phase, must be a minimum of several million years. This clearly sets a lower limit to the overall time scale for star formation and the lifetime of molecular clouds

Some empirical estimates of the H2 formation rate in photon-dominated regions

We combine recent ISO observations of the vibrational ground state lines of H2 towards Photon-Dominated Regions (PDRs) with observations of vibrationally excited states made with ground-based telescopes in order to constrain the formation rate of H2 on grain surfaces under the physical conditions in the layers responsible for H2 emission. We use steady state PDR models in order to examine the sensitivity of different H2 line ratios to the H2 formation rate Rf. We show that the ratio of the 0-0 S(3) to the 1-0 S(1) line increases with Rf but that one requires independent estimates of the radiation field incident upon the PDR and the density in order to infer Rf from the H2 line data. We confirm the earlier result of Habart et al. (2003) that the H2 formation rate in regions of moderate excitation such as Oph W, S140 and IC 63 is a factor of 5 times larger than the standard rate inferred from UV observations of diffuse clouds. On the other hand, towards regions of higher radiation field such as the Orion Bar and NGC 2023, we derive H2 formation rates consistent with the standard value. We find also a correlation between the H2 1-0 S(1) line and PAH emission suggesting that Rf scales with the PAH abundance. With the aim of explaining these results, we consider some empirical models of the H2 formation process. Here we consider both formation on big (a~0.1 microns) and small (a~10 Angstroms) grains by either direct recombination from the gas phase or recombination of physisorbed H atoms with atoms in a chemisorbed site. We conclude that indirect chemisorption is most promising in PDRs. Moreover small grains which dominate the total grain surface and spend most of their time at relatively low temperatures may be the most promising surface for forming H2 in PDRs.Comment: A&A in press, 16 pages, 5 figure

Concise Reporting of Benign Endometrial Biopsies is an Acceptable Alternative to Descriptive Reporting

In the United Kingdom, endometrial biopsy reports traditionally consist of a morphologic description followed by a conclusion. Recently published consensus guidelines for reporting benign endometrial biopsies advocate the use of standardized terminology. In this project we aimed to assess the acceptability and benefits of this simplified "diagnosis only" format for reporting non-neoplastic endometrial biopsies. Two consultants reported consecutive endometrial biopsies using 1 of 3 possible formats: (i) diagnosis only, (ii) diagnosis plus an accompanying comment, and (iii) the traditional descriptive format. Service users were asked to provide feedback on this approach via an anonymized online survey. The reproducibility of this system was assessed on a set of 53 endometrial biopsies among consultants and senior histopathology trainees. Of 370 consecutive benign endometrial biopsies, 245 (66%) were reported as diagnosis only, 101 (27%) as diagnosis plus a brief comment, and 24 (7%) as diagnosis following a morphologic description. Of the 43 survey respondents (28 gynecologists, 11 pathologists, and 4 clinical nurse specialists), 40 (93%) preferred a diagnosis only, with 3 (7%) being against/uncertain about a diagnosis only report. Among 3 histopathology consultants and 4 senior trainees there was majority agreement on the reporting format in 53/53 (100%) and 52/53 (98%) biopsies. In summary, we found that reporting benign specimens within standardized, well-understood diagnostic categories is an acceptable alternative to traditional descriptive reporting, with the latter reserved for the minority of cases that do not fit into specific categories. This revised approach has the potential to improve reporting uniformity and reproducibility

ROBO: a Model and a Code for the Study of the Interstellar Medium

We present ROBO, a model and its companion code for the study of the interstellar medium (ISM). The aim is to provide an accurate description of the physical evolution of the ISM and to set the ground for an ancillary tool to be inserted in NBody-Tree-SPH (NB-TSPH) simulations of large scale structures in cosmological context or of the formation and evolution of individual galaxies. The ISM model consists of gas and dust. The gas chemical composition is regulated by a network of reactions that includes a large number of species (hydrogen and deuterium based molecules, helium, and metals). New reaction rates for the charge transfer in $\mathrm H^+$ and $\mathrm H_2$ collisions are presented. The dust contains the standard mixture of carbonaceous grains (graphite grains and PAHs) and silicates of which the model follows the formation and destruction by several processes. The model takes into account an accurate treatment of the cooling process, based on several physical mechanisms, and cooling functions recently reported in the literature. The model is applied to a wide range of the input parameters and the results for important quantities describing the physical state of the gas and dust are presented. The results are organized in a database suited to the artificial neural networks (ANNs). Once trained, the ANNs yield the same results obtained by ROBO, with great accuracy. We plan to develop ANNs suitably tailored for applications to NB-TSPH simulations of cosmological structures and/or galaxies.Comment: accepted for publication in section 15. Numerical methods and codes of Astronomy and Astrophysic

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

Background: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. Methods: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. Findings: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). Interpretation: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. Funding: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership

Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset

Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial. Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included. Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye. Main Outcome Measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4–treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96. Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4–treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4–treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from −0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4–treated and sham-treated eyes was −0.01 logMAR (P = 0.89); the primary end point of a −0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4–treated and sham-treated eyes, respectively. Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes

Neutrino Physics from the Cosmic Microwave Background and Large Scale Structure

This is a report on the status and prospects of the quantification of neutrino properties through the cosmological neutrino background for the Cosmic Frontier of the Division of Particles and Fields Community Summer Study long-term planning exercise. Experiments planned and underway are prepared to study the cosmological neutrino background in detail via its influence on distance-redshift relations and the growth of structure. The program for the next decade described in this document, including upcoming spectroscopic galaxy surveys eBOSS and DESI and a new Stage-IV CMB polarization experiment CMB-S4, will achieve sigma(sum m_nu) = 16 meV and sigma(N_eff) = 0.020. Such a mass measurement will produce a high significance detection of non-zero sum m_nu, whose lower bound derived from atmospheric and solar neutrino oscillation data is about 58 meV. If neutrinos have a minimal normal mass hierarchy, this measurement will definitively rule out the inverted neutrino mass hierarchy, shedding light on one of the most puzzling aspects of the Standard Model of particle physics --- the origin of mass. This precise a measurement of N_eff will allow for high sensitivity to any light and dark degrees of freedom produced in the big bang and a precision test of the standard cosmological model prediction that N_eff = 3.046.Astronom

Inflation Physics from the Cosmic Microwave Background and Large Scale Structure

Fluctuations in the intensity and polarization of the cosmic microwave background (CMB) and the large-scale distribution of matter in the universe each contain clues about the nature of the earliest moments of time. The next generation of CMB and large-scale structure (LSS) experiments are poised to test the leading paradigm for these earliest moments---the theory of cosmic inflation---and to detect the imprints of the inflationary epoch, thereby dramatically increasing our understanding of fundamental physics and the early universe. A future CMB experiment with sufficient angular resolution and frequency coverage that surveys at least 1% of the sky to a depth of 1 uK-arcmin can deliver a constraint on the tensor-to-scalar ratio that will either result in a 5-sigma measurement of the energy scale of inflation or rule out all large-field inflation models, even in the presence of foregrounds and the gravitational lensing B-mode signal. LSS experiments, particularly spectroscopic surveys such as the Dark Energy Spectroscopic Instrument, will complement the CMB effort by improving current constraints on running of the spectral index by up to a factor of four, improving constraints on curvature by a factor of ten, and providing non-Gaussianity constraints that are competitive with the current CMB bounds.Astronom

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

Production of dust by massive stars at high redshift

The large amounts of dust detected in sub-millimeter galaxies and quasars at high redshift pose a challenge to galaxy formation models and theories of cosmic dust formation. At z > 6 only stars of relatively high mass (> 3 Msun) are sufficiently short-lived to be potential stellar sources of dust. This review is devoted to identifying and quantifying the most important stellar channels of rapid dust formation. We ascertain the dust production efficiency of stars in the mass range 3-40 Msun using both observed and theoretical dust yields of evolved massive stars and supernovae (SNe) and provide analytical expressions for the dust production efficiencies in various scenarios. We also address the strong sensitivity of the total dust productivity to the initial mass function. From simple considerations, we find that, in the early Universe, high-mass (> 3 Msun) asymptotic giant branch stars can only be dominant dust producers if SNe generate <~ 3 x 10^-3 Msun of dust whereas SNe prevail if they are more efficient. We address the challenges in inferring dust masses and star-formation rates from observations of high-redshift galaxies. We conclude that significant SN dust production at high redshift is likely required to reproduce current dust mass estimates, possibly coupled with rapid dust grain growth in the interstellar medium.Comment: 72 pages, 9 figures, 5 tables; to be published in The Astronomy and Astrophysics Revie